“Scientists have developed a drug to fight one of the fastest rising UK cancers,” The Mirror reported. It said that in a trial in 31 patients with skin cancers, tumours shrank by at least 30% in the first two weeks...

“Scientists have developed a drug to fight one of the fastest rising UK cancers,” TheMirror reported today. It said that in a trial in 31 patients with skin cancers, the tumours shrank by at least 30% in the first two weeks.

The study behind these stories is an early investigation of the safety and tolerability of a new drug (currently called PLX4032) in 31 patients with advanced melanoma. These findings have been presented at a cancer conference, but the research has not been published yet. The researchers say further, larger studies are planned.

Until larger trials with comparison groups are carried out, these findings, however significant, should be considered preliminary. The results are important, though, as there are few effective treatments for this type of cancer. It appears that a large proportion of the participants had a demonstrable response to the oral treatment in metastatic tumours in their lungs, bones, liver and stomach.

Where did the story come from?

The research was carried out by Dr P Chapman and colleagues from the Memorial Sloan-Kettering Cancer Centre in New York and other medical centres across the US and in Australia.

The study was presented at a joint conference held by the European Cancer Organisation and the European Society for Medical Oncology in Berlin. It has not yet been published in a peer-reviewed journal, and there is no indication from the conference abstract about funding.

What kind of scientific study was this?

This phase I trial tested the drug PLX4032, which is taken orally for the treatment of advanced metastatic melanoma. Phase I studies are early research of new treatments, and are carried out largely to establish the safety and appropriate doses of new drugs before they go on to larger studies that involve a comparison group.

The drug has been developed specifically for the treatment of advanced metastatic melanoma, a severe skin cancer that has proved very difficult to treat. The drug acts by blocking the activity of a cancer-causing mutation of the BRAF gene (which is thought to cause about 60% of melanomas). The BRAF gene codes for a protein that is important in regulating cell growth. When it mutates it can lead to cancer.

In this study, 31 people with melanoma and the BRAF mutation were given 960mg of PLX4032 twice a day in an oral form. Alongside safety and pharmokinetics (i.e. how the drug is absorbed in the body), the researchers assessed the anti-tumour effects based on certain criteria that depend on imaging of the tumour (using X-ray, CT or MRI). The criteria used to judge the response is known as RECIST (Response Evaluation Criteria in Solid Tumours), based primarily on the way the tumour shrinks in response to a treatment.

All of the patients had failed previous therapy (chemotherapy or treatment with Interleukin 2, and surgery).

What were the results of the study?

The study found that the maximum tolerated dose of the drug was 960mg twice a day. The results from 22 patients were available for analysis by the time this research was discussed at the conference. Of those, 14 were recorded as having partial responses (30% decrease in the longest diameter of target lesion for at least a month, and in the sum of these diameters if there were more than one lesion). Six other patients were reported to have shown some response but did not fulfil criteria for partial response.

These patients had advanced metastatic cancer and the BRAF mutation, and so the researchers looked at cancers that had spread from the original melanoma, including cancers in the liver, lung and bones and in the stomach and intestines. The researchers note responses in target lesions in these areas and also report that the response was associated with a "resolution of symptoms".

What interpretations did the researchers draw from these results?

The researchers say that they have established that the maximum tolerated dose of the new drug is 960mg twice a day and that in patients who had tumours with a BRAF mutation, the drug had demonstrated anti-tumour effects.

What does the NHS Knowledge Service make of this study?

This is a phase I trial and so is very early research. Larger studies are planned that should demonstrate the likely effective doses for the drug. The results in this small uncontrolled trial show that the new drug has an effect on specific types of advanced melanoma (that associated with BRAF mutation). There are some important points to consider when interpreting these findings:

Importantly, this treatment will only be relevant for people with melanoma who also have the BRAF gene mutation. Some 40% of melanoma patients do not have this mutation and the treatment investigated here will not be relevant for them. Studies in a non-selected population (i.e. people with and without BRAF mutations) will by definition have less positive responses because the drug is not a relevant treatment for some people.

None of the patients in the study had responded to previous therapies, including surgery, chemotherapy and treatment with Interleukin 2. For some people, these standard treatments are successful.

Survival or long-term response rates were not reported in this study.

The results are considered preliminary at this stage, particularly the efficacy results. The effects of treatment on survival have yet to be explored or demonstrated for the drug. Phase I studies such as this do not set out to compare new treatments with other approaches. The larger studies that follow this one will provide more information about how applicable the findings are to larger populations.

The results are significant. If they are repeated in larger studies then the drug may one day become a treatment for BRAF-related advanced melanoma, a cancer that has a poor prognosis and few other effective treatments when in an advanced stage.